Optimum Modification for the Highest Cytotoxicity of Cationized Ribonuclease

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Author(s)

    • Nukui Emiko NUKUI Emiko
    • Department of Bioscience and Biotechnology, Faculty of Engineering, Graduate School of Natural Science and Technology, Okayama University
    • KOSAKA Megumi
    • Department of Bioscience and Biotechnology, Faculty of Engineering, Graduate School of Natural Science and Technology, Okayama University
    • TADA Hiroko
    • Department of Bioscience and Biotechnology, Faculty of Engineering, Graduate School of Natural Science and Technology, Okayama University
    • SENO Masaharu
    • Department of Bioscience and Biotechnology, Faculty of Engineering, Graduate School of Natural Science and Technology, Okayama University
    • YAMADA Hidenori
    • Department of Bioscience and Biotechnology, Faculty of Engineering, Graduate School of Natural Science and Technology, Okayama University

Abstract

Cationization of a protein is considered to be a powerful strategy for internalizing a functional protein into cells. Cationized proteins appear to adsorb to the cell surface by electrostatic interactions, then enter the cell in a receptor- and transporter-independent fashion. Thus, in principle, all cell types appear to take up cationized proteins. Since ribonucleases (RNases) have a latent cytotoxic potential, cationized RNases could be useful cancer chemotherapeutics. In this study, we investigated the effect of the degree of cationization on the cytotoxicity of RNase A by modifying carboxyl groups with ethylenediamine. We found that there is an optimum degree of modification for cytotoxicity, in which 5 to 7 out of 11 carboxyl groups in RNase A are modified, toward MCF-7 and 3T3-SV 40 cells. More interestingly, the cytotoxicity of cationized RNase As correlates well with the value of [RNase activity] × [estimated concentration of RNase free from RNase inhibitor], mimicking the practical enzymatic activity of cationized RNase As in cytosol. The results indicate that cationization of a protein to an optimum level is important for maintaining protein function in the cytosol. Sophisticated protein cationization techniques will help to advance protein transduction technology.

Journal

  • The Journal of Biochemistry

    The Journal of Biochemistry 132(2), 223-228, 2002-08-01

    The Japanese Biochemical Society

References:  56

Cited by:  3

Codes

  • NII Article ID (NAID)
    10010650358
  • NII NACSIS-CAT ID (NCID)
    AA00694073
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    0021924X
  • NDL Article ID
    6254960
  • NDL Source Classification
    ZR2(科学技術--生物学--生化学)
  • NDL Call No.
    Z53-B472
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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